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Identifying Genetic Variants and Metabolites Associated with Rapid Estimated Glomerular Filtration Rate Decline in Korea Based on Genome–Metabolomic Integrative Analysis
Identifying the predisposing factors to chronic or end-stage kidney disease is essential to preventing or slowing kidney function decline. Therefore, here, we investigated the genetic variants related to a rapid decline in the estimated glomerular filtration rate (eGFR) (i.e., a loss of >5 mL/min...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695695/ https://www.ncbi.nlm.nih.gov/pubmed/36422279 http://dx.doi.org/10.3390/metabo12111139 |
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author | Lee, Sangjun Han, Miyeun Moon, Sungji Kim, Kyungsik An, Woo Ju Ryu, Hyunjin Oh, Kook-Hwan Park, Sue K. |
author_facet | Lee, Sangjun Han, Miyeun Moon, Sungji Kim, Kyungsik An, Woo Ju Ryu, Hyunjin Oh, Kook-Hwan Park, Sue K. |
author_sort | Lee, Sangjun |
collection | PubMed |
description | Identifying the predisposing factors to chronic or end-stage kidney disease is essential to preventing or slowing kidney function decline. Therefore, here, we investigated the genetic variants related to a rapid decline in the estimated glomerular filtration rate (eGFR) (i.e., a loss of >5 mL/min/1.73 m(2) per year) and verified the relationships between variant-related diseases and metabolic pathway signaling in patients with chronic kidney disease. We conducted a genome-wide association study that included participants with diabetes, hypertension, and rapid eGFR decline from two Korean data sources (N = 115 and 69 for the discovery and the validation cohorts, respectively). We identified a novel susceptibility locus: 4q32.3 (rs10009742 in the MARCHF1 gene, beta = −3.540, P = 4.11 × 10(−8)). Fine-mapping revealed 19 credible, causal single-nucleotide polymorphisms, including rs10009742. The pimelylcarnitine and octadecenoyl carnitine serum concentrations were associated with rs10009742 (beta = 0.030, P = 7.10 × 10(−5), false discovery rate (FDR) = 0.01; beta = 0.167, P = 8.11 × 10(−4), FDR = 0.08). Our results suggest that MARCHF1 is associated with a rapid eGFR decline in patients with hypertension and diabetes. Furthermore, MARCHF1 affects the pimelylcarnitine metabolite concentration, which may mediate chronic kidney disease progression by inducing oxidative stress in the endoplasmic reticulum. |
format | Online Article Text |
id | pubmed-9695695 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96956952022-11-26 Identifying Genetic Variants and Metabolites Associated with Rapid Estimated Glomerular Filtration Rate Decline in Korea Based on Genome–Metabolomic Integrative Analysis Lee, Sangjun Han, Miyeun Moon, Sungji Kim, Kyungsik An, Woo Ju Ryu, Hyunjin Oh, Kook-Hwan Park, Sue K. Metabolites Article Identifying the predisposing factors to chronic or end-stage kidney disease is essential to preventing or slowing kidney function decline. Therefore, here, we investigated the genetic variants related to a rapid decline in the estimated glomerular filtration rate (eGFR) (i.e., a loss of >5 mL/min/1.73 m(2) per year) and verified the relationships between variant-related diseases and metabolic pathway signaling in patients with chronic kidney disease. We conducted a genome-wide association study that included participants with diabetes, hypertension, and rapid eGFR decline from two Korean data sources (N = 115 and 69 for the discovery and the validation cohorts, respectively). We identified a novel susceptibility locus: 4q32.3 (rs10009742 in the MARCHF1 gene, beta = −3.540, P = 4.11 × 10(−8)). Fine-mapping revealed 19 credible, causal single-nucleotide polymorphisms, including rs10009742. The pimelylcarnitine and octadecenoyl carnitine serum concentrations were associated with rs10009742 (beta = 0.030, P = 7.10 × 10(−5), false discovery rate (FDR) = 0.01; beta = 0.167, P = 8.11 × 10(−4), FDR = 0.08). Our results suggest that MARCHF1 is associated with a rapid eGFR decline in patients with hypertension and diabetes. Furthermore, MARCHF1 affects the pimelylcarnitine metabolite concentration, which may mediate chronic kidney disease progression by inducing oxidative stress in the endoplasmic reticulum. MDPI 2022-11-19 /pmc/articles/PMC9695695/ /pubmed/36422279 http://dx.doi.org/10.3390/metabo12111139 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lee, Sangjun Han, Miyeun Moon, Sungji Kim, Kyungsik An, Woo Ju Ryu, Hyunjin Oh, Kook-Hwan Park, Sue K. Identifying Genetic Variants and Metabolites Associated with Rapid Estimated Glomerular Filtration Rate Decline in Korea Based on Genome–Metabolomic Integrative Analysis |
title | Identifying Genetic Variants and Metabolites Associated with Rapid Estimated Glomerular Filtration Rate Decline in Korea Based on Genome–Metabolomic Integrative Analysis |
title_full | Identifying Genetic Variants and Metabolites Associated with Rapid Estimated Glomerular Filtration Rate Decline in Korea Based on Genome–Metabolomic Integrative Analysis |
title_fullStr | Identifying Genetic Variants and Metabolites Associated with Rapid Estimated Glomerular Filtration Rate Decline in Korea Based on Genome–Metabolomic Integrative Analysis |
title_full_unstemmed | Identifying Genetic Variants and Metabolites Associated with Rapid Estimated Glomerular Filtration Rate Decline in Korea Based on Genome–Metabolomic Integrative Analysis |
title_short | Identifying Genetic Variants and Metabolites Associated with Rapid Estimated Glomerular Filtration Rate Decline in Korea Based on Genome–Metabolomic Integrative Analysis |
title_sort | identifying genetic variants and metabolites associated with rapid estimated glomerular filtration rate decline in korea based on genome–metabolomic integrative analysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695695/ https://www.ncbi.nlm.nih.gov/pubmed/36422279 http://dx.doi.org/10.3390/metabo12111139 |
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